Journal of Korean Neurosurgical Society

  • 제67권4호
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  • Pages.418-430
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  • 2024
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  • 2005-3711(pISSN)
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  • 1598-7876(eISSN)
대한신경외과학회 (The Korean Neurosurgical Society)
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Potential Risk of Choline Alfoscerate on Isoflurane-Induced Toxicity in Primary Human Astrocytes

  • Hyun Jung Lee (Department of Anesthesiology and Pain Medicine, College of Medicine, Ewha Womans University) ;
  • Hye Rim Cho (Department of Neurosurgery, Korea University Medicine, Korea University College of Medicine) ;
  • Minji Bang (Photo-Theranosis and Bioinformatics for Tumor Laboratory, Research Institute for Future Medicine, Samsung Medical Center) ;
  • Yeo Song Lee (Department of Neurosurgery, Korea University Medicine, Korea University College of Medicine) ;
  • Youn Jin Kim (Department of Anesthesiology and Pain Medicine, College of Medicine, Ewha Womans University) ;
  • Kyuha Chong (Photo-Theranosis and Bioinformatics for Tumor Laboratory, Research Institute for Future Medicine, Samsung Medical Center)
  • 투고 : 2023.10.05
  • 심사 : 2023.10.19
  • 발행 : 2024.07.01
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초록

Objective : Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods : This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 µM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results : A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 µM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 µM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion : The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.

키워드

과제정보

We would like to thank Dae Hye Shin and Hae Young Ko for their sincere support and assistance. We would also like to thank Editage (www.editage.co.kr) for English language editing. This work was supported by funding from the National Research Foundation of the Republic of Korea (NRF2020R1C1C1010686 and NRF-2019M3A9E2061791).

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